Τομέας ΦΑΡΜΑΚΕΥΤΙΚΗΣ ΧΗΜΕΙΑΣ
Library of the School of Science

2012-09-20

2012

Τσοτάκος Θεόδωρος

Γεώργιος Φώσκολος Καθηγητής Ε.Κ.Π.Α. (Επιβλέπων), Ιωάννης Πιρμεττής Ερευνητής Α’ Ε.Κ.Ε.Φ.Ε «Δημόκριτος», Γεώργιος Φυτάς Καθηγητής Ε.Κ.Π.Α.

Σύμπλοκα του Τεχνητιου-99m με παράγωγα λιπαρών οξέων

Greek

Aiming at the synthesis and characterization of novel neutral rhenium and
technetium complexes of the general formula fac-[Μ(CO)3(ΧΥΖ)] and fac-[Μ(CO)
3(ΧΥ)(Ζ)], where Μ=Re or 99mTc, XYZ: tridentate ligand, XY: bidentate ligand,
Z: monodentate ligand, and the biological evaluation of the 99mTc complexes for
heart’s metabolism imaging, we report herein the synthesis and characterization
of a series of fatty acids’ derivatives functionalized at the ω-site by
cysteine, benzimidazole-thiabutanoic acid, dithiocarbate or isonitrile
moieties. Cysteine and benzimidazole-thiabutanoic acid derivatives act as
tridentate ligands to the metal core [fac-M(CO)3]+ (Μ=Re or 99mTc) at oxidation
state (I) being able to strongly coordinate through the SNO system of donor
atoms. Dithiocarbamate derivatives act as bidentate ligands to the metal core
being able to strongly coordinate through the SS system of donor atoms.
Isonitrile derivative acts as monodentate ligand.
The rhenium complexes were synthesized using the organometallic precursor [Εt4N]
2[ReBr3(CO)3] and they were fully characterized by elemental analysis, IR and
NMR spectroscopy. The analogous complexes at tracer level (99mTc) were
synthesized using the cationic precursor [99mTc(H2O)3(CO)3]+. The 99mTc
complexes were characterized by comparative HPLC using the analogous well
characterized rhenium complexes as reference.
Stability studies showed that the 99mTc complexes are stable (in the reaction
mixture or isolated, as well as in the presence of cysteine and histidine) up
to 6 hours after labeling. In human plasma and in liver and kidney homogenates
the 99mTc complexes demonstrated sufficient stability. Lipophilicity studies
showed that the 99mTc complexes were lipophilic.
Biodistribution experiments in normal mice, showed that the 99mTc complexes
demonstrated high initial heart uptake and sufficient retention. They are
excreted mainly through the hepatobilliary system.
Metabolites’s study showed that the fatty acid analogues are catabolized
(partially or totally), possibly through b-oxidation.

Fatty acids, Technetium-99m, Rhenium, Cardiac metabolism, SPECT

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https://pergamos.lib.uoa.gr/uoa/dl/object/1309372